DESCRIPTION: The major emphasis of this project revolves around the role that flavoprotein quinone reductases may play in antitumor quinone cytotoxicity. The first enzyme to be investigated is DT-diaphorase and the applicant wishes to determine its role in the response of human tumors to antitumor quinones. Within this objective the applicant will study the expression and function of an alternatively spliced DT- diaphorase product. The second theme of this grant application is the study of the Thioredoxin/Thioredoxin Reductase (T/TR) system. The applicant wishes to focus upon the effects that antitumor quinones have upon this system, the levels of T/TR in human tumors, the role of T/TR in cell growth and transformation, the role of T/TR is the redox control of transcription factor activity, and the role of T/TR in apoptosis or programmed cell death.